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益气养阴方抗血管生长抑制肿瘤转移及对肿瘤相关基因表达谱的影响

Study on Anti-Metastasis Mechanisms of Reinforcing Qi and Nourishing Yin Through Angiogenesis Inhibition Effect and Gene Expression Profile Analysis

【作者】 孙静

【导师】 李震;

【作者基本信息】 山东中医药大学 , 中西医结合基础, 2008, 博士

【摘要】 目的:探讨益气养阴方抗血管生长抑制肿瘤转移及对肿瘤相关基因表达谱的影响。方法:复制CAM模型及肿瘤自发性和实验性(包括血道、淋巴道)转移模型,运用免疫组织化学、基因芯片等技术,对益气养阴方作用不同瘤株荷瘤小鼠的抑瘤率、转移抑制率和血液流变学指标,以及抑制血管生长和肿瘤基因表达谱的改变等指标进行检测和研究。结果:CAM模型显示本方通过降低肿瘤细胞VEGF及MMP-2的表达而抑制肿瘤血管生长:不同瘤株转移模型显示本方可以抑制肿瘤自发性、实验性血道和淋巴道转移;血液流变学指标改变证实本方改善肿瘤机体的血液高粘状态;差异基因表达谱分析表明本方对与肿瘤浸润转移、信号转导、细胞增殖、细胞凋亡及与代谢有关等多个靶位基因进行调节。结论:益气养阴方具有抗血管生长抑制肿瘤转移的作用,其机制是通过改善血液流变学指标、降低VEGF、MMP-2的表达以及通过调控肿瘤相关基因的表达而实现的。

【Abstract】 Objective To explore the mechanisms of Reinforcing Qi and Nourishing Yin in inhibiting tumor metastasis. Methods By duplicating tumor spontaneous and experimental models separately and using immunohistochemical technique and gene chips, some indexes were observed in tumor-bearing mice treated by Reinforcing Qi and Nourishing Yin, including tumor inhibition rate. Inhibition rate of metastasis, changes of hemorheology, effects on tumor angiogenesis and the expression of tumor metastasis-related genes. Results Reinforcing Qi and Nourishing Yin could inhibit tumor spon-taneous and experimental haemato-genous metastasis and lymphatic metastasis. Hemorheology showed that it could improve blood high viscosity in tumors. Experiments of CAM indicated that this decoction could reduce the expression of VEGF and MMP-2 in tumor cells, thus inhibiting tumor angiogenesis. The analysis of gene expression spectrum revealed that it could regulate multiple target genes such as tumor filtration and metastasis, signal transduction, cell proliferation, apop-tosis and metabolism-related genes. Conclusion It is demonstrated that Reinforcing Qi and Nourishing Yin has the effect of anti-tumor metastasis. Improving hemorheological conditions, reducing the expression of VEGF and MMP-2 and regulating the expression of tumor metastasis-related genes may be the key mechanisms.

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